title: Cell death in the myocardium: my heart won't go on.
abstract: Loss of cardiomyocytes plays a critical role in the pathogenesis of heart failure. With fewer myocytes, the heart is unable to sustain efficient contraction. Much attention has been focused on understanding mechanisms of cell death in myocytes with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Both necrosis and apoptosis contribute to loss of myocytes, and this loss of cells is a hallmark of cardiac pathologies, including ischemia/reperfusion, myocardial infarction, and heart failure. Apoptosis is a highly regulated process that is activated via death receptors in the plasma membrane or via permeabilization of the mitochondria. Necrosis is generally viewed as an uncontrolled process that leads to mitochondrial swelling, cell rupture, and subsequent inflammation. However, recent studies have uncovered a signaling pathway that mediates regulated necrosis or necroptosis. Mitochondria play an important role in both apoptosis and necrosis, and changes in their morphology can affect the cells' susceptibility to stress. This review focuses on the various modes of cell death in the myocardium and highlights how they contribute to loss of myocytes in response to stress.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Amabel M
authors.initials: AM
authors.lastname: Orogo
authors.forename: Åsa B
authors.initials: ÅB
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D006333:Heart Failure / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D008929:Mitochondria, Heart / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D009336:Necrosis / Q000473:pathology; D053218:Receptors, Death Domain / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D035683:MicroRNAs; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D053218:Receptors, Death Domain
keywords: apoptosis; cardiovascular disease; cell death; mitochondria; signal transduction